1-aminophenyl-4h-s-triazolo(4,3-a)(1,4)benzodiazepines

ABSTRACT

WHEREIN R AND R0 ARE DEFINED AS ABOVE, IN AN ORGANIC SOLVENT, TO GIVE THE COMPOUNDS OF FORMULA II ABOVE. THE COMPOUNDS OF FORMULA II ABOVE, AND THE PHARMACOLOGICALLY ACCEPTABLE ACID SALTS THEREOF ARE SEDATIVE AND TRANQUILIZING REAGENTS.   R0-N(-R)-C6H4-CO-NH-NH2   WHEREIN R1, R2, R3, R4, AND R5 ARE DEFINED AS ABOVE, WITH AN AMINOBENZOYL HYDRAZINE OF THE FORMULA III   BENZODIAZEPINE   2-(S=),3-R1,5-(R2,R3-PHENYL),R4,R5-1,3-DIHYDRO-2H-1,4-   AND WHEREIN R2, R3, R4, AND R5 ARE SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL DEFINED AS ABOVE, AMINO, HALOGEN, NITRO, CYANO, TRIFLUOROMETHYL, AND ALKOXY, ALKYLTHIO, ALKYLSULFONYL, AND ALKYLSULFINYL, ALKANOYLAMINO, IN WHICH THE CARBON MOIETY IS OF 1 TO 3 CARBON ATOMS, INCLUSIVE, AND DIALKYLAMINO, IN WHICH THE ALKYL GROUP IS DEFINED AS ABOVE. THE PROCESS OF THIS INVENTION CONSISTS IN HEATING A 1,3DIHYDRO-5-PHENYL-2H-1,4-BENZODIAZEPINE-2-THIONE OF THE FORMULA I   -COOCH2CH2CH3; WHEREIN R AND R0 ARE SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL OF 1 TO 3 CARBON, ATOMS, INCLUSIVE, AND ALKENYL OF 3 TO 4 CARBON ATOMS, INCLUSIVE; WHEREIN R1 IS SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL DEFINED AS ABOVE, -COOCH3, -COOC2H5, AND   TRIAZOLO(4,3-A)(1,4)BENZODIAZEPINE   1-(R0-N(-R)-C6H4-),4-R1,6-(R2,R3-PHENYL),R4,R5-4H-S-   1 - (AMINOPHENYL) - 6 - PHENYL - 4H - S - TRIAZOLO(4,3-A) (1,4)BENZODIAZEPINES OF THE FORMULA II:

United States Patent 3,743,652 l-AMINOPHENYL-4H-s-TRIAZOL0[4,3-a][1,4] BENZODIAZEPINES Robert B. Moliett, Kalamazoo, Mich., assignor to The Upjohn Company, Kalamazoo, Mich.

No Drawing. Filed Nov. 2, 1971, Ser. No. 194,911 Int. Cl. C07d 5.7/02 US. Cl. 260308 R 3 Claims ABSTRACT OF THE DISCLOSURE 1 (aminophenyl) 6 phenyl 4H s triazolo [4,3-a] [1,4]benzodiazepines of the Formula II:

wherein R and R are selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon, atoms, inclusive, and alkenyl of 3 to 4 carbon atoms, inclusive; wherein R is selected from the group consisting of hydrogen, alkyl defined as above, COOCH COOC H and and wherein R R R and R are selected from the group consisting of hydrogen, alkyl defined as above, amino, halogen, nitro, cyano, trifluoromethyl, and alkoxy, alkylthio, alkylsulfonyl, and alkylsulfinyl, alkanoylamino, in which the carbon moiety is of 1 to 3 carbon atoms, inclusive, and dialkylamino, in which the alkyl group is defined as above.

The process of this invention consists in heating a 1,3- dihydro-S-phenyl-ZH-1,4-benzodiazepine-2-thione of the Formula I H i N R R R4 1 wherein R R R R and R are defined as above, with an aminobenzoyl hydrazide of the Formula III wherein R and R are defined as above, in an organic solvent, to give the compounds of Formula II above.

The compounds of Formula II above, and the pharmacologically acceptable acid salts thereof are sedative and tranquilizing reagents.

BACKGROUND OF THE INVENTION Field of the invention This invention is directed to new organic compounds and is particularly concerned with novel l-aminophenyl- Patented July 3, 1973 6 phenyl s-triazolo[4,3-a][l,4]benzodiazepines and a process for the production thereof.

The novel compounds and the process of production therefor can be illustratively represented as follows.

HIS

1 III R3 R0 N R N N R N a Rs R wherein R and R are selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, and alkenyl of 3 to 4 carbon atoms, inclusive; wherein R is selected from the group consisting of hydrogen, alkyl defined as above, COOCH -COOC H and COOCH CH CH DESCRIPTION OF THE PREFERRED EMBODIMENT Lower alkyl groups of 1 to 3 carbon atoms, inclusive, are exemplified by methyl, ethyl, propyl, and isopropyl.

The carbon chain moiety of alkoxy, alkylsulfinyl, alkylsulfonyl, and alkylthio, which is of 1 to 3 carbon atoms, inclusive, can be defined as lower-alkyl of 1 to 3 carbon atoms, inclusive, as above.

The alkanoylamino group of 1 to 3 carbon atoms consists of formamido (sari...)

acetamido and propionamido.

The term halogen includes fluorine, chlorine, and bromine.

The novel compounds of the Formula II and pharmacologically acceptable addition salts thereof have sedative, hypnotic, anticonvulsant, tranquilizing, and muscle relaxant effects in mammals and birds. Also as feed additives they increase growth rate and feed efiiciency of livestock and poultry.

The pharmacologically acceptable acid addition salts of compounds of Formula II contemplated in this invention, are the hydrochlorides, hydrobromides, hydroiodides, sulfates, phosphates, cyclohexanesulfamates, methanesulfonates, acetates, toluenesulfonates, lactates, tartrates, citrates, malates, maleates, and the like, prepared by reacting a compound of Formula II with the selected pharmacologically acceptable acid.

Sedative efiects of l-(p-aminophenyl)-8-chloro-6-phenyl-4H-s-thiazolo[4,3-a] [1,4]benzodiazepine are shown by the following tests in mice:

Chimney test: [Med. Exp. 4, 145 (1961)]: The effective intraperitoneal dosage for 50% of mice (ED is 11 mg./kg. The test determines the ability of mice to back up and out of a vertical glass cylinder within 30 seconds. At the effective dosage, 50% of the mice failed doing it.

Dish test: Mice in Petri dishes (10 cm. diameter, cm. high, partially embedded in wood shavings), climb out in a very short time, when not treated. Mice remaining in the dish for more than 3 minutes indicates tranquilization. ED equals the dose of test compound at which 50% of the mice remain in the dish. The ED (intraperitoneal administration) in this test was 1.8 mg./kg.

Pedestal test: The untreated mouse leaves the pedestal in less than a minute to climb back to the floor of the standard mouse box. Tranquilized mice will stay on the pedestal for more than 1 minute. The ED (intraperitoneal administration) is mg./kg.

Nicotine antagonism test: Mice in a group of 6 are injected with the test compound l-(p-aminopheny1-8- chloro 6 phenyl-4H-s-triazolo[4,3-a][l,4]benzodiazepine). Thirty minutes later the mice including control (untreated) mice are injected with nicotine salicylate (2 mg./kg.). The control mice show over-stimulation, i.e., (1) running convulsions followed by (2) tonic extensor fits; followed by (3) death. An intraperitoneal dosage of 3.6 mg./kg. of the test compound protected 50% of the mice against (2) and (3) (ED Antagonism to strychnine (as sulfate): The effective dosage ED of l-(p-aminophenyl)-8-chloro-6-phenyl- 4H-s-triazolo[4,3-a][1,4]benzodiazepine is 2.5 mg./ kg. orally in mice. The test consists in orally administering into groups of 6 mice the test compound, l-(p-arninophenyl) 8 chloro 6 phenyl-4H-s-triazolo[4,3-a] [1,4] benzodiazepine, and 30 minutes later 3 mg./kg. strychnine sulfate intraperitoneally. The survivors after 4 hours reflect the activity of the compound as a muscle relaxant and antispasmodic. A dosage of 3 mg./kg. of strychnine sulfate is routinely fatal to all the control mice.

The pharmaceutical forms contemplated by this invention include pharmaceutical compositions suited for oral, parenteral, and rectal use, e.g., tablets, powder packets, cachets, dragees, capsules, solutions, suspensions, sterileinjectable forms, suppositories, bougies, and the like. Suitable diluents or carriers such as carbohydrates (lactose), proteins, lipids, calcium phosphate, cornstarch, stearic acid, methylcellulose and the like may be used as carriers or for coating purposes. Water or oil, e.g., coconut oil, sesame oil, safiiower oil, cottonseed oil, peanut oil, may be used for preparing solutions or suspensions of the active drug. Sweetening, coloring, and flavoring agents may be added.

For mammals and birds food premixes, with starch, oatmeal, dried fishmeat, fishmeal, flour, and the like can be prepared. A feed containing from 10-500 g. per ton of feed of compound II or salts thereof is useful to produce faster growth, or higher milk or egg production in farm animals.

As tranquilizer the compounds of Formula II its pharmacologically acid addition salts and N-oxides thereof can be used in dosage of ill-20.0 mg./kg in oral or injectable preparations as described above, to alleviate tension and anxiety in mammals, or birds, such as e.g., occurs when animals are in travel.

Other acid addition salts of the compounds of Formula II can be made such as the fluosilicic acid addition salts which are useful mothproofing compounds or the trichloroacetates useful as herbicides against Johnson grass, Bermuda grass, yellow foxtail, and green foxtail, and quack grass.

The starting materials of Formula I of this invention, substituted or unsubstituted 1,3 dihydro 5 phenyl- ZH 1,4 benzodiazepine- 2 thiones, are described by G. A. Archer and L. H. Sternbach [J. Org. Chem. 20, 231 (1964) and U8. Pat. 3,422,091]. These compounds (I) are made by the reaction of the known substituted or unsubstituted 1,3 dihydro 5 phenyl 2H 1,4- benzodiazepin-Z-ones by heating with phosphorus pentasulfide in pyridine for about 45 minutes (Archer et al., ibid.). The following compounds of Formula I are representative starting materials:

1,3-dihydro-5-phenyl-2H-1,4-benzodiazepine-Z-thione;

6-chloro-1,3-dihydro-5-(m-bromophenyl)-2H-l,4-benzodiazepine-Z-thione;

7-chloro- 1, 3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2- thione;

8-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2- thione;

7-bromol, 3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2- thione;

7-chloro-1,3-dihydro-5-(3,4-dimethy1phenyl)-2H-1,4-

benzodiazepine-2-thione;

l, 3dihydro-5- (2-methyl-4-methoxyphenyl) -2H- 1,4-

benzodiazepine-Z-thione;

9-brorno-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2- thione;

7-methyl-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepine- 2-thione;

7-nitro- 1, 3 -dihydro-5-phenyl-2H- 1,4-benzodiazepine- 2-thione;

7 -fluoro- 1, 3-dihydro-5-phenyl-2H-1,4-benzodiazepine- 2-thione;

7-trifluoromethyll, 3-dihydro-5-phenyl-2H-1,4-benzodiazepine-Z-thione;

9-trifluoromethy1-1,3-dihydro-5- [p- (propionylamino) phenyl]-2H-1,4-benzodiazepine-Z-thione;

7-cyano- 1, 3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2- thione;

8-cyano- 1, 3-dihydro-5- [p- (trifiuoromethyl phenyl] -2H- 1,4benzodiazepine-2-thione;

7-chloro-1,3-dihydro-5-(o-chlorophenyD-ZH-1,4-benzodiazepine-Z-thione;

6-ethy1thio-1,3-dihydro-5- (o-bromophenyl)-2H- 1,4-

benzodiazepine-Z-thione;

6, S-dichloro-1,3-dihydro-5-(o-tluorophenyD-ZH-1,4-

benzodiazepine-Z-thione 8-propoxy-7-bromo-1,3-dihydro-5- [m-(ethylsulfinyl) phenyl] -2H- l,4-benzodiazepine-2-thione;

9-diisopropylamino-7-methyl- 1, 3-dihydro-5- [mpropylsulfonyl) phenyl] -2H- 1,4-benzodiazepine-2-thione;

7-bromo-1,3-dihydro-5- (o-fluorophenyl)-2H-1,4-benzodiazepine-Z-thione;

3 -methyl- 1, 3-dihydro-5- (ofiuorophenyl) -2H-1,4-benzodiazepine-Z-thione;

7-fluoro-1,3-dihydro-5-(o-fiuorophenyl) -2H-1,4-benzopine-2-thione;

3 -methyl- 1, 3 -dihydro-5 (p-fluorophenyD-ZH-1,4-benzodiazepine-Z-thione;

7-nitro-1,3-dihydro-5-(o-chlorophenyl)-2H-1,4-benzodiazepine-Z-thione;

S-nitro-l ,3-dihydro-5- (o-chlorophenyl) -2H- l,4-benzodiazepine-Z-thione;

7-bromo-1,3-dihydro-5-(o-bromophenyl) -2H-1,4-benzodiazepine-2-thione;

7-methylsulfinyl- 1,3-dihydro-5- (o-fluorophenyl) -2H-1,4-

benzodiazepine-Z-thione;

7-methyl-1,3-dihydro-5-(o-ch1orophenyl)-2H-1,4-benzodiazepine-Z-thione;

7-methylthio-1, 3-dihydro-5-phenyl-2H-1,4-benzodiazepine-Z-thione;

7-cyano1,3-dihydro-5-(ochlorophenyl)-2H-1,4-benzodiazepine-Z-thione;

3,6,8-trimethyl-1,3-dihydro-5-(o-chlorophenyl)-2H-1,4-

benzodiazepine-Z-thione;

9-propylsulfonyl-7-methyll, 3-dihydro-5-phenyl-2H-1,4-

benzodiazepine-Z-thione;

7-trifiuoromethyl- 1, 3-dihydro-5- (o-chlorophenyl -2H- 1,4-benzodiazepine-Z-thione;

7-dimethylamino-1,3-dihydro-S-phenyl-2H-1,4-benzodiazepine-Z-thione;

7-fluoro- 1, 3-dihydro-5- (o-chlorophenyl )-2H-1,4-benzodiazepine-Z-thione;

7 ,S-dicyano- 1,3-dihydro-5- [p- (methylsulfonyl) phenyl] 2H-1,4-benzodiazepine-2-thione;

6,9-dichloro-1,3-dihydro-5-(p-isopropylphenyl)-2H-1,4-

benzo diazepine-Z-thione;

6,8-diethyl-1,3-dihydro-5- (m-ethylphenyl) -2H-1,4-benzodiazepine-Z-thione;

6-nitro-1,3-dihydro-5-(o-cyanophenyl) -2-H-1,4-benzodiazepine-Z-thione 7 ,9-bis (dipropylamino) 1,3-dihydro-5- (o-nitrophenyl) 2H-1,4-benzodiazepine-Z-thione;

9-acetylamino-1,3-dihydro-5- (p-cyanophenyl)-2H-1,4-

benzo diazepine-Z-thione;

and the like.

In carrying out the process of the invention, a selected 1,3 dihydro 5-phenyl-2H-1,4-benzodiazepine-2-thione (I) in an inert organic solvent, preferably in an alkanol, e.g., methanol, ethanol, l-propanol, 2-propanol, l-butanol, Z-butanol, 1,1-dimethylethanol, hexanol, ethoxyethanol, or the like is heated to between 60160 C., with the selected aminobenzoyl hydrazide:

defined as above.

The reaction can be followed by the IR or NMR if desired, and elevated pressures (sealed tube or autoclave) can be used to facilitate closure of the triazole ring at a convenient rate.

In the preferred embodiment of this invention the acid hydrazide is used in excess such as from 1.1 to 4 times the theoretically required amount, in an inert atmosphere. The reaction is, however, operative with smaller or larger amounts of hydrazide. The reaction period is between 1 and 48 hours. At the termination of the reaction the reaction mixture can be evaporated to give a crude product consisting of the desired l-(aminophenyl)-6-phenyl- 4H-s-triazolo[4,3-a][l,4]benzodiazepine (II). The crude Compound II is then purified by standard methods, e.g., extraction, chromatography, and/ or recrystallization from. solvents such as ethyl acetate, methylene chloride, chloroform, acetonitrile or the like.

The following examples are illustrative of the processes and products of the present invention, but are not to be construed as limiting.

EXAMPLE 1 1- (p-aminophenyl -8-chloro-6-phenyl-4H-s-triazolo [4,3-a] [1,4-] benzodiazepine A mixture of 6.31 g. (0.002 mole) of 7-chloro-1,3-dihydro-S-phenyl-ZH-l,4-benzodiazepine-2-thione and 10.0 g. (0.066 mole) of p-aminobenzoyl hydrazide in 175 ml. of l-butanol was stirred, under nitrogen, at reflux for 14 hours. Most of the solid dissolved, then other solid separated and finally this solid redissolved. On cooling some excess hydrazide separated and was removed by filtration. The filtrate was evaporated to dryness in vacuo and the residue was dissolved in 90 ml. of methanol. This solution was poured into 400 ml. of water giving a gummy precipitate which soon solidifed. This was collected,

washed with water, dried, and recrystallized from 500 ml. of 2-propanol yielding 7.0 g. of nearly white, fiufiy needles of melting point 257-267 C. (after sintering at and recrystallizing at -210). This product was found to contain 2-propanol. It was dissolved in dilute aqueous hydrochloric acid, filtered, and precipitated with ammonium hydroxide. The solid was collected, washed with water, dried, and recrystallized from 2-propanol and dried at 100/ l mm. for 17 hours to give 4.9 g. of l-(paminophenyl) 8 chloro 6 pheuyl 4H s triazolo [4,3-a] [l,4]benzodiazepine (48%) of melting point 266- 269 C.

AnaIysis.Calcd. for C H CIN (percent): C, 68.48; H, 4.18; Cl, 9.19; N, 18.15. Found (percent): C, 68.19; H, 4.68; CI, 9.15; N, 18.34.

EXAMPLE 2 l-[p- (N-methylamino)phenyl] -8-chloro-6-(o-chlorophenyl)-4H-s-triazolo [4,3-a] [1,4]benzodiazepine In the manner given in Example 1, 7-chloro-l,3-dihydro-5-(o-chlorophenyl)-2H-1,4,-benzodiazepine-2 thione and p-[N-methylamino1benzoyl hydrazide can be heated in l-butanol to give 1-[p-(N-methylamino)phenyl]-8- chloro 6 (o chlorophenyl) 4H s triazolo[4,3-a] [1,4] benzodiazepine.

EXAMPLE 3 1-[p-(N-dimethylamino)phenyl]-8-chloro-6-(2,6-difluor0- phenyl)-4H-s-triazolo [4,3-a] [1,4] benzodiazepine In the manner given in Example 1, 7-chloro-1,3-dihydro 5 (2,6 difluorophenyl) 2H 1,4 benzodiazepine-Z-thione and p-(N-dimethylamino)benzoyl hydrazide can be heated in 2-butanol to give l-[p-(N-dimethylamino)phenyl] 8 chloro 6 (2,6 difluorophenyl)- 4H-s-triazolo [4,3-a] [1,4] benzodiazepine.

EXAMPLE 4 1- [p- (N-diethylamino phenyl] -8-nitro-6- (o-chloropheny1)-4H-s-triazolo[4,3-a] [1,4] benzodiazepine In the manner given in Example 1, 7 nitro-1,3-dihydro 5 (o chlorophenyl) 2H 1,4 benzodiazepine- 2-thione and p-(N-diethylamino)benzoyl hydrazide can be heated in 2-propanol to give l-[p-(N-diethylamino)- phenyl] 8 nitro 6 (o chlorophenyl) 4H s triazolo [4,3-a] [1,4]benzodiazepine.

EXAMPLE 5 1- [m-(N-isopropylamino phenyl] -7-ethylthio-6- (o-bromophenyl -4H-s-triazolo [4,3-a] [1,4] benzodiazepine In the manner given in Example 1, 6-ethylthio-1,3-dihydro 5 (o brornophenyl) 2H 1,4 benzodiazepine-2-thione and m-(N-isopropylamino)benzoyl hydrazide can be heated in l-butanol to give l-[m-(N-isopropylamino)phenyl] 7 ethylthio 6 (o bromophenyl) -4H-s-triazolo [4,3-a] [1,4] benzodiazepine.

EXAMPLE 6 1 (p aminophenyl 9 trifluoromethyl 6 [(p propionylamino)phenyl] 4H s triazolo[4,3 a][1,4]- benzodiazepine In the manner given in Example 1, 9-trifiuoromethyl- 1,3 dihydro 5 [(p propionylamino)phenyl] 2H- l,4-benzodiazepine-2-thione and p-aminobenzoyl hydrazide can be heated in l-butanol to give 1-(p-aminophenyl)- 9 trifluoromethyl 6 [(p propionylamino)phenyl]- 4H-s-triazolo [4,3-a] [1,4]benzodiazepine.

EXAMPLE 7 1 [p (N dipropylamino)phenyl] 8,9 dicyano-6- [p- (methylsulfonyl)phenyl] 4H s triazolo[4,3-a] [1,4] benzodiazepine In the manner given in Example 1, 7,8-dicyano-1,3- dihydro 5 [(p methylsulfonyl)phenyl] 2H 1,4-ben- 7 zodiazepine-Z-thione and [p-(N-dipropylamino)benzoyl] hydrazide can be heated in ethanol to give l-[p-(N-dipropylamino)phenyl] 8,9 dicyano 6 [(P methylsulfonyl)phenyl] 4H s triazolo[4,3-al] [1,4]benzodiazepine.

EXAMPLE 8 l-(o-aminophenyl)-7,9-diethyl-6-(m-ethylphenyl) -4H- s-triazolo [4,3-a] [1,4] benzodiazepine In the manner given in Example 1, 6,8-diethy1-1,3-dihydro 5 (m ethylphenyl) 2H 1,4 benzodiazepine 2- thione and (o-amino)benzoyl hydrazide can be heated in l-propanol to give 1-(o-aminophenyl)-7,9-diethy1-6-(methylphenyl -4H-s-triazolo [4,3-a] [1,4] benzodiazepine.

EXAMPLE 9 1- (N-methylamino phenyl] -7-nitro-6- o-cyano phenyl) -4H-s-triazolo [4,3-a] [1,4] benzodiazepine In the manner given in Example 1, 6-nitro-1,3-dihydro (0 cyanophenyl) 2H 1,4 benzodiazepine- Z-thione and p-(N-methylamino)benzoyl hydrazide can be heated in 2-ethoxyethanol to give l-[o-(N-methylamino)phenyl] 7 nitro 6 (o-cyanophenyl) 4H-striazolo [4,3-a] 1,4] benzodiazepine.

EXAMPLE 1 [p (N dimethylamino)phenyl] 4,7,9 trimethyl- 6 (o chlorophenyl) 4H s triazolo[4,3-a][1,4]- benzodiazepine In the manner give in Example 1, 3,6,8-trimethyl-1,3- dihydro 5 (o chlorophenyl) 2H 1,4 benzodiazepine-Z-thione and p-(N-dimethylamino)benzoyl hydrazide can be heated in 1,1-dimethylethanol to give l-[P-(N-dimethylamino) phenyl] 4,7,9 trimethyl 6 (o chlorophenyl) -4H-s-triazolo [4,3-a] 1,4] benzodiazepine.

In the manner given in Example 1, other l-aminophenyl 4H s triazolobenzodiazepines of Formula H can be produced by heating together a selected 1,3-dihydro 5 phenyl 2H 1,4 benzodiazepine 2 thione 1 with an ,aminobenzoyl hydrazide III. Representative compounds of Formula II, thus produced, include:

1- (m-aminophenyl) -8-chloro-6- 3,4-dimethylphenyl) 4H-s-triazolo [4, 3-a] 1,4] benzodiazepine;

1- [o( N-ethylamino) phenyl] -10-bromo-6-phenyl-4H- s-triazolo [4,3-a] 1,4] benzodiazepine;

1- [p- (N,N-diethylamino) phenyl] -7,9-dichloro-6- (ofiuorophenyl) -4H-s-tn'azolo [4,3 -a] 1,4] benzodiazepine;

1- p- N,N-dipropylamino) phenyl] -9-propoxy- 8-bromo- 6- [m- (ethylsulfonyl phenyl] -4H-s-triazolo [4,3-a] [1,4] benzodiazepine;

1- [p- (N,N-diisopropylamino) phenyl] -4-methyl-6- (ofluorophenyl -4H-s-tri azolo 4,3 -a] 1,4] benzodiazepine 1- (p-aminophenyl) 10-propylsulfonyl-6-phenyl4H-striazolo[4,3-a] [1,41benzodiazepine;

1- o-aminophenyl) -8-methylsulfinyl-6- (o-fiuorophenyl -4H-s-triazolo[4,3-a] 1,4] benzodiazepine;

1- [m- (N,N-dimethylamino) phenyl] -4-carbethoxy-6- .(o-chlorophenyl-4H-s-triazolo [4,3-a] 1,4] benzodiazepine;

1- (o-aminophenyl) -7-bromo-4-carbopropoxy-6-(pethylphenyl) -4H-s-triazolo 4,3-a] 1,4] benzodiazepine;

1-[p-(N,N-diallylamino)phenyl]-8-cyano-4-propyl-6- (o-chlorophenyl) -4H-s-triazolo [4,3-a] 1,4] benzodiazepine;

1- [p- (-N-crotylamino phenyl] -8-trifluoromethyl-6- ochlorophenyl) -4H-s-triazolo [4,3-a] 1,4] benzodiazepine;

1- [m- (N-methylarnino) phenyl] -8-dimethylamino-6- phenyl-4H-s-triazolo[4,3-a] [1,41benzodiazepine 8 1- [o- (N-propylamino) phenyl] -6- (2-methyl-4-methoxyphenyl) -4H-s-triazolo [4,3-a] [1,4] benzodiazepine;

and the like.

Treating the compounds of Formula 'II with pharmacologically acceptable acids such as hydrochloric, hydrobromic, phosphoric, sulfuric acetic, propionic, toluenesulfonic, mcthanesulfonic, tartaric, citric, lactic, malic, maleic, cyclohexanesulfamic acids produces the pharmacologically acceptable salts of these compounds of Formula H which can be used like the free base compound of Formula II. Salt formation is achieved in conventional manner by reacting the compounds of Formula II with excess of a selected acid in a suitable medium e.g. water, a lower alkanol, ether, or acetone and recovering the salt by evaporating the solvent, preferably in vacuo.

I claim:

1. A compound selected from the group consisting of a 1 aminophenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine of the Formula 11 wherein R and R are selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, and alkenyl of 3 to 4 carbon atoms, inclusive, wherein R is selected from the group consisting of hydrogen, alkyl defined as above, COOCH -OOOC H and wherein R R R and R are selected from the group consisting of hydrogen, alkyl defined as above, amino, halogen, nitro, cyano, trifluoromethyl, and alkoxy, alkylthio, alkylsulfonyl, and alkylsulfinyl, alkanoylamino, in which the carbon moiety is of 1 to 3 carbon atoms, inclusive, and dialkylamino, in which the alkyl group is defined as above, and the pharmacologically acceptable acid addition salts of II.

2. A compound according to claim 1 wherein R, R R R R and R are hydrogen, the group is in p-position, R is 8-chloro and the compound is therefore l-(p-aminophenyl)-8-chloro-6-phenyl-4H-s-triazolo- [4,3-a] [1,4]benzodiazepine. I

3. A compound according to claim 1, wherein R, R R R and R are hydrogen, R is o-chloro, R is 8- chloro, the group is in p-position and the compound is therefore, l-(paminophenyl)-8-chloro-6-(o-chlorophenyl) 4H s-triazo [4,3-a] 1,4] benzodiazepine.

References Cited FOREIGN PATENTS 2,012,190 3/1970 Germany 260-308 R ALTON D. ROLLINS, Primary Examiner U.S. Cl. X.R.

71-92; 992 G, 2 T; 260239.3 D, 558 A; 424269 

